DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. The amendment, filed 02/23/26, has been entered. Claims 23-25, 30-33, and 37-38 are pending and under examination. Claims 1-22, 26-29, and 34-36 are cancelled. Claims 23 and 38 are amended.
Claim Interpretation
3. In the interest of compact prosecution, it is noted that:
Applicant has significantly changed the invention by swapping 3 of the original 5 required bacterial species to new, different species; however, it remains the Office’s position that the specification does not meet the requirements of 35 U.S.C. 112(a) for either the combination of the first 5 species, or the combination of the new 5 species (see maintained rejections below).
Withdrawal of Objections/Rejections
4. The following are withdrawn from the Office Action, filed 09/23/26:
The rejection of claims 23-25, 30-33, and 37-38 under 35 U.S.C. 112(b) as being indefinite, found on page 36 at paragraph 12, is withdrawn in light of Applicant’s amendments thereto.
New Objection
5. Claim 23 is objected to because of the following informalities: awkward language rendering the claim difficult to read. For example: claim 23 reads “… wherein the at least 5 species of bacteria are selected from …” followed by a list of only 5 species. In order to avoid confusion with regards to combinations and sub-combinations (see repeated argument in Remarks, page 8), the Office recommends “… wherein the at least 5 species of bacteria are …” followed by the 5 species. In addition, claim 23 recites “…and treating the human subject for autism by administering to the subject a composition …” in which “the human subject” is repeated. The Office recommends deleting the second recitation. Regardless, appropriate correction is required.
Maintained Rejection: Claim Rejections - 35 USC § 112
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
7. Claims 23-25, 30-33, and 37-38 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
As amended, independent claim 23 is drawn to method(s) of diagnosing and treating autism in a human subject with IBS, comprising determining an abundance of at least 5 species of bacteria in a sample from the subject, wherein the at least 5 species of bacteria are now identified as Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea, and wherein a diagnosis of autism is made when the abundance of the at least 5 species of bacteria in the sample from the human subject is significantly lower than the abundance of each of the at least 5 species of bacteria in a sample derived from a reference population; and treating the human subject for autism by administering to the subject a composition to the human subject which increases the abundance of the at least 5 species of bacteria that differs in abundance between the sample from the human subject and the sample derived from the reference population. However, despite the change in 3 of the 5 particular species, it remains the Office' s position that methods of diagnosing and treating autism in a subject with IBS (see claims 23-25, 30-32, and 37-38) and/or methods of monitoring the effectiveness of treating autism in a subject with IBS (see claim 33) have not been described with sufficient particularity, such that one skilled in the art would recognize that Applicant had possession of the claimed invention, at the time of filing, because of (A) a lack of a correlation, known or disclosed, between the claimed functional requirements (i.e. the ability to diagnose and treat autism in a subject with IBS) and the structures that meet those requirements (i.e. using these 5 specific species of bacteria having a lower abundance as compared to a poorly described “reference population” to accurately make a diagnosis of autism and then subsequently treat autism in subjects with IBS); and/or (B) a lack of a representative number and variety of species (i.e. there are zero disclosed examples bearing sufficient resemblance to the claims for diagnosing and treating autism in a subject with IBS as no individual was actually diagnosed with and/or treated for autism based on as little as the lower abundance of 5 particular species including Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea) to constitute possession of the claimed genus.
For example, with regards to claim 23, the specification does not adequately describe how to use as little as 5 specific bacterial species (i.e. now identified as Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea), haphazardly picked off a list of 50 in Table 22, and (i.e. now not even the top 5 of the 50); and that are otherwise not correlated with autism (e.g. see state of the art below) for a diagnosis of autism in a subject having IBS as compared to an individual with autism and not having IBS and/or an individual with IBS but not autism and/or individual without autism or IBS because, inter alia, the reference population and/or the model used are not adequately described. For example, the specification does not adequately describe the reference population needed to make the comparisons in the claims because paragraph [0078] suggests the skilled artisan has to generate their own reference population first, in order to practice the claimed methods, which even a highly skilled artisan would easily recognize as affecting any outcomes achieved (i.e. the reference population is an essential feature to practice the claimed method, but has not adequately been described). In addition, the specification states that age is the most significant difference in microbial profiles between individuals (see [0127; 0150]) but does not adequately describe age data (or strata) for the populations of those with and without autism, and/or with and without IBS, such that a diagnosis of autism could be predictably and accurately made and then treated. The specification does not adequately describe what “treating” even encompasses. Therefore, the specification does not adequately describe methods as claimed in claim 23, and by extension, the methods of linking claim 33. Accordingly, it remains the Office’s position that the specification does not adequately described these methods with sufficient particularity, such that one skilled in the art would recognize that Applicant had possession of the claimed invention.
Further, with specific regards to claims 24 and 25, the specification does not adequately describe what is to be done with data from the additional 10, or additional 20 species’ abundances. It is also noted that there is no requirement in the claims (and insufficient guidance in the specification) on how much different (i.e. magnitude and/or direction) the additional 10-20 bacterial species’ abundances would need to be for the diagnosis to be made and/or how to integrate these abundances - required by claims 24 or 25 - into the method of claim 23. Thus, the specification does not adequately describe the additional steps required by dependent claims 24 and 25. Similarly, with specific regards to claim 38, the claim requires determining the abundance of at least one additional species, but there is no requirement in the claims (and insufficient guidance in the specification) on how different (i.e. direction and/or magnitude) the one or more species would need to be and/or how to integrate this information into the method of claim 23 to contribute to a diagnosis of autism (or not). Accordingly, it remains the Office’s position that the specification does not described these additional method steps, with sufficient particularity, such that one skilled in the art would recognize that Applicant had possession of the claimed invention.
In addition, the specification does not adequately describe methods of treating autism comprising administering compositions that would increase the abundance of the 5 newly selected particular species (i.e. switched to: Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea) or how increasing the relative abundances of these 5 species thereby treats autism. The specification does not even define what treating autism would even encompass. Accordingly, the specification does not provide adequate written description support for methods of treating autism in general (see claim 23), or by administering a nutraceutical, probiotic, or FMT, specifically (i.e. see dependent claims 30, 31, and 32). It is noted that Example 12 and Table 24 report “treating” IBS with a probiotic but this is not the same as treating autism; thus, the specification does not adequately describe treating autism. It is also noted that, as amended, claim 23 now requires all 5 of the named species to be increased by “a composition” that is administered, but claim 33 subsequently only requires any one of them to increase (and/or even decrease) as indicative of the effectiveness of such treatment. Regardless, the specification does not adequately describe either because the specification does not adequately describe treating autism. Further, the specification does not adequately describe what the administered composition would require such that it could target these five newly chosen claimed species and predictably increase each and/or all. The specification does not adequately describe what the relative increase and/or decrease is compared to, for example, to the same reference population as in claim 23, or is the comparison to the individual’s earlier results? Thus, the specification does not adequately describe compositions for treating autism in a subject with IBS, as required by the claims. By extension, the specification also does not provide an adequate description for monitoring the effectiveness of any treatments for autism in a subject with IBS because the treatments and/or compositions per se have not been adequately described (see claim 33). Accordingly, the limitation “…wherein an increase and/or decrease in the abundance of one or more species of bacteria is indicative of the effectiveness of the treatment” is not adequately supported by the application as filed.
Therefore, it remains the Office’s position that the specification does not adequately describe methods of diagnosing and treating autism, in general, or in subjects with IBS, specifically, by merely determining and comparing the abundances of Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea and consequently, at best, the specification amounts to a mere wish for possession of an invention that may not even exist; emphasis added; see MPEP 2163 and Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
However, MPEP §2163 states that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance (as in the instant case), the disclosure must describe a sufficient variety of species to reflect the variation within that genus. In the instant case, the specification appears to describe “Diagnosis of Autism” (see Example 5) but merely states that “The model, using default settings and species level abundance, predicted Autism correctly for nearly all individuals except two individuals” (see page 41). However, the claims are not limited to this model and the model is not adequately described (i.e. What were the default settings? Which of the species were used? All of the species or as little as 5? Which 5: the formerly claimed combination or the newly identified combination?) and thus the specification does not provide adequate written description support for methods of diagnosing, treating, and/or evaluating treatment in subjects with autism and IBS, using as little as a relatively lower abundance of this particular combination of 5 species (e.g. Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea; indiscriminately chosen from a list of 40 or 50; and which are not otherwise correlated with autism as evidenced by the state of the art, below), in any sample, by any means, either in general or in individuals with IBS because neither the reference population or the model are adequately described. The specification provides a table of 40 bacterial species/strains identified as “The most informative genera used in the Random Forest model for predicting Autism” (Table 7), but does not provide sufficient guidance with regards to the Random Forest model and/or how these 40 species are used to diagnose autism in individuals with IBS. However, newly required species Eubacterium desmolans is not even listed in Table 7. Further, it is noted that Example 11 states “A Random Forest algorithm was used to identify the most indicative species of bacteria” (see Tables 22 and 23); but again, the claims are not limited to this model and the specification does not adequately describe the model and/or how the mean relative abundances were calculated (i.e. compared to what reference population?). Therefore, it remains the Office’s position that the specification does not provide adequate written description for a genus of methods for diagnosing and treating autism in subjects with IBS comprising as little as the use of lower relative abundances of an undisclosed particular combination (i.e. see new matter rejection below) of 5 claimed bacteria (e.g. was Eubacterium hallii, Eubacterium rectale, Lachnobacterium bovis, Lachnoclostridium glycyrrhizinilyticum, and Blautia glucerasea, see paragraph [0038] but now switched to: Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea, with no such corresponding embodiment or explanation).
In addition, the specification states that the human microbiota consists of several trillion microorganisms, most of which are of bacterial origin and are non-pathogenic (see [0002]); and although there is a growing body of evidence to suggest that dysbiosis of the human microbiota is associated with a number of diseases, it remains difficult to determine or predict the exact impact that the microbiota has on human health and its involvement in human disease, due to the highly complex interplay between bacterial species in the microbiota (e.g. see [0003]; emphasis added). Thus, the specification provides evidence that the use of bacterial abundance data, in general, or the use of as little as a reduced amount of 5 haphazardly selected species, to diagnose and treat autism was still under development and thus necessarily unpredictable.
Accordingly, the specification lacks the necessary, and adequately described, structures (i.e. how these 5 specific species of bacteria when lower in abundance as compared to what reference population and/or using what defaults in what Random Forest model) to predictably function (i.e. diagnose and treat autism in subjects with IBS) as is claimed. There are no adequately disclosed structure-function correlation(s) and, based on that lack of information within the specification, there is evidence that a representative number and a representative variety of species have not yet been identified (e.g. for the originally claimed combination of 5 bacterial species and/or the newly claimed combination of 5 bacterial species). Therefore, it remains the Office’s position that even one of skill in the art would not conclude that Applicant was in possession of the genus claimed.
With regards to the state of the art, methods for diagnosing autism in subjects, with or without IBS, using microbial profiles, were under development, and thus were necessarily unpredictable, as evidenced by, the art of record.
For example, Srikantha et al. 2019 (The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorders; International Journal of Molecular Sciences; 20: 1-28). Srikantha teaches new research points to a possible link between autism spectrum disorders and gut microbiota (see abstract), but does not teach art-recognized methods for diagnosing autism using as little as a change in abundance of 5 particular species of bacteria. Srikantha teaches there are no satisfactory effective treatments available for autism (i.e. not a predictable art; e.g. page 2, second paragraph). Srikantha teaches there are conflicting reports regarding the microbial compositions in autistic children (i.e. teaches the art does not agree upon or recognize structure-function correlations; e.g. section 5.1 and Figure 3).
Similarly, Dan et al. 2020 (Altered gut microbial profile is associated with abnormal metabolic activity of Autism Spectrum Disorder; Gut Microbes 11(5): 1246-1267) teaches accumulating evidences demonstrates that gastrointestinal (GI) symptoms, such as gaseousness, diarrhea, and constipation, often co-occurred with ASD core symptoms in children with ASD; that recent studies have shown that changes in gut microbiota can modulate the gastrointestinal physiology, immune function, and even behavior through the gut-microbiome-brain axis; and these co-occurring gastrointestinal symptoms have prompted researchers to examine the gut microbial composition of ASD children and determine their potential role in promoting and reflecting ASD symptoms (see introduction and Figure 1). Dan teaches that compared to a control group, the ASD group displayed alternation of gut microbiota composition, including ASD showed less genera including Prevotella and Megamonas; and Escherichia-Shigella, Dialister, and Bifidobacterium were increased in ASD and that consistent with other studies that reported changes in microbiome associated with constipated populations, significant increases in the abundance of Coprobacter, Barnesiella, and Veillonella were found, but that Fusobacterium was reduced; and suggests the possibility that specific microbial patterns may be linked to constipation symptoms of specific disease, which suggests the necessity to more deeply understand the ASD-related gastrointestinal symptoms as they pertain to diagnosis and treatment of ASD (see Figures 5, 7 and Discussion). Thus, Dan supports methods for diagnosing and treating autism using microbial abundance data and/or profiles was under development and thus necessarily unpredictable.
Similarly, Olbjorn et al. 2019 (Fecal microbiota profiles in treatment-naïve pediatric inflammatory disease associations with disease phenotype, treatment, and outcome; Clinical and Experimental Gastroenterology 37-49; DOI: 10.2147/ CEG.S186235; of record) teaches Eubacterium hallii and Eubacterium rectale are associated with IBS (e.g. see table S1 and page 43); and therefore those subjects in Olbjoorn’s research paper, with a detectable reduction of E. halii (for example) would, using Applicant’s invention, risk be incorrectly diagnosed with and treated for autism. Thus, Olbjorn supports methods for diagnosing and treating autism using microbial abundance data and/or profiles was under development and thus necessarily unpredictable.
In addition, the state of the art does not recognize diagnosing or treating autism using microbial abundance data (i.e. the state of the art is unpredictable) but does recognize that miss diagnosing autism is harmful, as evidenced by, for example, Yates et al. 2016 (Diagnosing autism/autism spectrum disorders; Paediatrics and Child Health 26(12): 513-518) which teaches that to maximize detection and minimize harm it is essential for all clinicians working with children to have a sound knowledge of the presentation and assessment (i.e. diagnosis) of autism spectrum disorders (i.e. miss-diagnosing an ASD is harmful; see abstract). Yates teaches there are at least two international classification systems for diagnosing ASD comprising the use of a range of specifiers with the recognition that severity may vary with time and environmental context so should not be used to determine eligibility for and provision of services; and teaches specifiers including whether there is intellectual disability, language impairment, other associated disorders or comorbidities e.g. medical, genetic, mental or behavioral (see page 513, first page). Yates teaches ASD is a heterogeneous condition with no single pathognomonic feature or specific diagnostic test; and that diagnosis can be challenging as affected individuals display variation in the degree of behavioral severity, language and intellectual abilities (i.e. is unpredictable; see page 514). Yates teaches that age is an important factor in diagnosing autism (page 514, right column). Accordingly, Yates supports that the state of the art is unpredictable (i.e. under development and not agreed upon) and does not recognized diagnosing autism using microbial abundance data, but does recognize miss diagnosing is harmful and that age is an important consideration.
Similarly, Huang et al. 2020 (Diagnosing of autism in adulthood: A scoping review; Autism 24(6): 1311-1327) teaches adult autism assessment involves unique challenges because diagnosis relies on knowledge of developmental history, adults and families' lack of access to early medical records and inaccurate recall of developmental milestones which become significant difficulties (i.e. is unpredictable; e.g. see abstract and introduction). Huang teaches that considering the complex mental health needs of individuals diagnosed in adulthood and emotional reactions following diagnosis the lack of formal support after diagnosis is of concern especially as diagnostic services often do not provide ongoing support a collaborative multidisciplinary effort is needed to create support pathways after diagnosis and that even adults who were assessed but not diagnosed with autism would also benefit from counselling and mental health support due to high rates of mental illness and reported negative reactions following assessment (i.e. miss-diagnosing an ASD is real because of the uncertainty and has harmful consequences). Accordingly, Huang also supports that the state of the art is unpredictable and does not recognized diagnosing autism using microbial abundance data, but does recognize miss diagnosing is harmful.
Finally, Kong et al. (2021) Nutrients 13, 1552 (submitted by Applicant) teaches the etiology of autism remains elusive and effective treatments are still largely unavailable (see Introduction, first paragraph) and that despite promising preliminary findings, the underlying mechanisms and causal relationships of such synergistic effects (i.e. for treatments) remain elusive and deserve further investigation in additional trials (i.e. still under development; e.g. see section 5, conclusions). Accordingly, Kong supports that the state of the art regarding treating autism is still under development and not agreed upon, and thus necessarily unpredictable.
Consequently, neither the specification (e.g. no disclosed structure-function correlations and no representative species) nor the state of the art (e.g. no art-recognized structure-function correlations) provides sufficient written description to support the genus encompassed by the claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Given the above analysis of the factors as a whole, which the courts have determined are critical in determining whether Applicant is in possession of the claimed invention, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
Applicant’s Arguments and Response to Arguments
8. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For example:
With regards to the argument that the claims, as amended, specify that the relative abundance of each of the 5 bacterial species in the subject to be tested is lower in the subject than the reference population; and accordingly, the Examiner's questions have been addressed in the amended claims (see Remarks, page 5); The Office agrees that the amendments addressed some of the issues raised in the rejection, but notes that the amendments do not address other issues, such as how - as little as 5 species, and now not even the top 5 species, predictably diagnose and treat autism in a subject with IBS and/or what the reference population needs to be and/or what model (and parameters) are used and/or what to do with the other 1 to 20 abundances of which species, changed in what way? Thus, this argument is not persuasive because it does not address all of the issues raised in the rejection. Further, Applicant is reminded of earlier remarks in which they clearly stated that the bacterial species recited in Table 22 are listed in order of importance and the top 5 species listed in Table 22 are the same 5 species recited in claim 23 (see Remarks, filed 5/13/25); yet, Applicant changed the 5 species away from the “top 5” in Table 22, to what appears to be an indiscriminate selection including swapping 3 different species (i.e. now the combination is not made of the top 5), and thus, it remains the Office’s position that the specification, as filed, does not adequately describe methods for diagnosing and treating autism in a subject with IBS comprising the use of the relatively lower abundances of as little as these 5 particular species of bacteria.
With regards to the argument that the bacterial species were identified by the present inventors by comparing samples derived from a subject having IBS without autism, to samples derived from a subject having IBS with autism; and that this analysis identified the most indicative bacterial species for determining whether a subject with IBS has autism (see Table 22; i.e. that these five were all lower than subjects with IBS but without autism; see Remarks, pages 5-6); it is noted that the original invention relied upon the top 5 ranked species, but as currently amended, the method relies on a new, different combination of 5 species that have been haphazardly selected out of the 50 species on a list, further supporting the Office’s position that the specification as filed, does not adequately describe methods for diagnosing and treating autism in a subject with IBS comprising the use of as little as the relative abundances of five species, since this combination was not even envisaged at the time of filing (i.e. for comparison, see [0038]). Thus, this argument is not persuasive because (1) correlation does not equate to causation; and/or (2) switching the 5 claimed species away from the top 5 and toward a different and apparently indiscriminate collection of 5, supports that the specification does not adequately support the methods as claimed.
With regards to the argument that the skilled person [does not?] need to know details of the reference sample used, apart from the fact that it was derived from a subject having IBS without autism and thus in order to work the invention, a skilled person will be able to obtain their own reference population as a matter of routine (see Remarks, page 6 with “does not” added by Examiner for compact prosecution – otherwise this argument would support the Office’s position); the Office disagrees and notes that the reference population is essential to make the comparison and that the specification states that it was age that was the most significant difference in microbial profiles between individuals (see [0127; 0150]) but does not adequately describe age data (or strata) for the populations of those with and without autism such that a diagnosis of autism in a subject with IBS could be made. This is also supported by the art which teaches the importance of age (e.g. see Yates). Thus, this argument is not persuasive because the reference population, to which the comparison is required to be made, is required in order to practice the claimed method, but it is not adequately described, as set forth above.
With regards to the arguments and assertions that a skilled person would understand that the average relative abundance is used to measure a fold change between the reference population and the autism population because this is a common method in microbiome and compositional studies to compare how much a feature or in this case species changes between conditions relative to the total composition; and that calculating the fold change from average relative abundance is a valid and common approach interpreted as a relative change; and that the use of the average relative abundance implies that there must be a range; and any skilled person using this type of analysis would know this; and that using the average relative abundance allows for lower, higher or not detected in a sample from a person with IBS-Autism relative to the reference population (see Remarks, pages 6-7, emphasis added); the Office again notes the explicit importance of the reference population, which has not be adequately described; and further notes that ranges and/or fold changes are not required (nor adequately described). Thus, these arguments are not persuasive because they support the Office’s position that the specification is deficient. For example, looking at one of the
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claimed species, the abundance reported varies over at least an order of magnitude.
Thus, if the relative abundance of Eubacterium hallii is determined to be greater than 0.000783435 (see first dashed arrow) but lower than 0.001865504 (second dashed arrow) – is a diagnosis made? The specification does not adequately describe what to do with this situation; thus, it remains the Offices’ position that the specification is not sufficient to satisfy the requirements of 35 U.S.C. 112(a).
With regards to the argument that available probiotics or nutraceuticals are well-known and it would be routine for a skilled person to determine which readily available probiotics or nutraceuticals would be useful for treating the autism diagnosed by the present invention (see Remarks, page 7); the Office notes that the particular probiotic and/or nutraceutical would need to target and increase the 5 particular species and that this increase thereby treats autism; and that this (i.e. treatment via increasing these 5 particular species) is not adequately described. Therefore, this argument is not persuasive because no subjects were actually diagnosed and/or treated for autism and/or monitored for treatment using the relative abundance data from as little as five particular species and even an ordinary artisan would recognize that autism is not treated (i.e. which Applicant did not define anyway) with probiotics, as evidenced by the state of the art (see above). Thus, this argument also supports the Office’s position because it demonstrates a fundamental piece of the method (i.e. treating autism) amounts to merely a wish for the invention; see MPEP 2163 and Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); emphasis added; In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"); emphasis added.
Therefore, all of Applicant’s arguments have been fully considered, but none were found persuasive. Accordingly, it remains the Office’s position that methods of diagnosing and treating autism in a subject with IBS and/or methods of monitoring the effectiveness of treating autism in a subject with IBS have not been described with sufficient particularity, such that one skilled in the art would recognize that Applicant had possession of the claimed invention, at the time of filing, because of (A) a lack of a correlation, known or disclosed, between the claimed functional requirements (i.e. the ability to diagnose autism, and treat autism, and/or monitor treatments of autism in a subject with IBS) and the structures that meet those requirements (i.e. using these 5 specific species of bacteria having a lower abundance as compared to a poorly described “reference population” and/or a poorly describe model); and/or (B) a lack of a representative number and variety of species (i.e. there are zero disclosed examples bearing sufficient resemblance to the claims for diagnosing and treating autism in a subject with IBS, as no individual was actually diagnosed or treated with autism based on as little as the lower abundance of 5 particular species) to constitute possession of the claimed genus.
Accordingly, it remains the Office’s position that Applicant has not satisfied the requirements of 35 U.S.C. 112(a).
Maintained Rejection: Claim Rejections - 35 USC § 112
9. Claims 23-25, 30-33, and 37-38 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Factors to be considered in determining whether undue experimentation is required, are set forth in In re Wands, 8 USPQ2d 1400. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and (8) the breadth of the claims. Although all the factors were considered, the most relevant ones are discussed below. In the instant case:
Nature of the invention: The nature of the invention encompasses method(s) of diagnosing and treating autism in a human subject with IBS, comprising determining an abundance of at least 5 species of bacteria in a sample from the subject, wherein the at least 5 species of bacteria are (now) Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea, and wherein a diagnosis of autism is made when the abundance of the 5 species of bacteria in the sample from the human subject is significantly lower than the abundance of each of the 5 species of bacteria in a sample derived from a reference population; and treating the human subject for autism by administering to the subject a composition to the human subject which increases the abundance of the at least 5 species of bacteria that differs in abundance between the sample from the human subject and the sample derived from the reference population.
Accordingly, it remains the Office’s position that undue experimentation would be required to practice the claimed invention, with a reasonable expectation of success, because it would not be predictable from the disclosure of one particular example what other examples may or may not work; see MPEP 2164.03. In the instant case, there are no adequately disclosed examples bearing sufficient resemblance to any of the methods claimed (i.e. no subjects were actually diagnosed and/or treated for autism using the abundance data from as little as five particular species and/or no reference population is disclosed and/or the model is insufficiently described).
Breadth of the claims: The broadest reasonable interpretation of the claims covers numerous, diverse methods for diagnosing, treating, and monitoring treatments for autism in subjects with IBS, using as little as the relative abundance data of 5 bacterial species (i.e. amended to change the combination to: Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea) that are not otherwise correlated with autism (e.g. see state of the art below), from any sample, using any means of determining abundance, and wherein if the abundance data of all five species in that sample is significantly lower than a reference population, then a diagnosis of autism is made. However, because of the lack of guidance provided, even a skilled artisan would have to start from scratch and first determine which reference populations, which samples, using which means, and using which models and with what parameters, would predictably lead to an accurate diagnosis of autism in a subject with IBS, and then determine which treatment methods would reliably increase the otherwise undisclosed combination of five particular species, and in what amounts, and compared to what (e.g. to the same reference population or to a different one, or to the subject’s first set of results) to reliably treat autism (i.e. which is not defined) to thereby practice the methods as claimed. But, even “treating” autism has not been sufficiently disclosed or defined. The skilled artisan would have to figure out and assemble the poorly described “reference” population to which to compare results from the subjects with IBS to determine if a diagnosis should be made (or not). The skilled artisan would have to figure out “default settings” of a Random Forest model to generate similar results for the five species haphazardly selected from a list of 50 as found on one table (i.e. see Table 22) but not another (i.e. see Table 7). In addition, the skilled artisan would have to figure out what to do with each additional piece of abundance data in dependent claims 24, 25 and 38 in order to achieve the goal(s) of the preamble(s). Accordingly, undue experimentation would be required to practice the claimed invention, with any reasonable expectation of success, because while enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed and such guidance has not been provided.
Amount of direction provided by Inventor and Existence of Working Examples: The specification states that the human microbiota consists of several trillion microorganisms, most of which are of bacterial origin and are non-pathogenic (see [0002]); and although there is a growing body of evidence to suggest that dysbiosis of the human microbiota is associated with a number of diseases, it remains difficult to determine or predict the exact impact that the microbiota has on human health and its involvement in human disease, due to the highly complex interplay between bacterial species in the microbiota (e.g. see [0003]). Thus, the specification provides evidence that the use of bacterial abundance data to diagnose and treat autism, with or without IBS, was still under development and thus necessarily unpredictable. The specification appears to disclose “Diagnosis of autism” (see Example 5) but merely states that “The model, using default settings and species level abundance, predicted Autism correctly for nearly all individuals except two individuals” (see page 41). However, the claims are not limited to this model and the model is not sufficiently disclosed (e.g. What were the default settings? Which species were included?) and thus does not provide support for methods of diagnosing, treating, and/or evaluating treatment in subjects with autism and IBS, using as little as a difference in 5 particular species, which are not otherwise correlated with autism, in general, or with individuals with IBS and autism (e.g. see state of the art below). The specification provides a table of 40 bacterial species/strains identified as “The most informative genera used in the Random Forest model for predicting Autism” (Table 7), but does not provide sufficient guidance with regards to how these 40 species are used to diagnose autism in individuals with IBS. It is also noted that this table does not include the newly amended species (e.g. Eubacterium desmolans). Thus, the specification does not sufficiently disclose how to use the abundance data to predictably make an accurate diagnosis of autism and does not sufficiently disclose how to treat autism (or what that even encompasses) with relative abundances of 5 particular bacterial species. In addition, Example 11 states “A Random Forest algorithm was used to identify the most indicative species of bacteria” (see Tables 22 and 23); but the claims are not limited to this model and the specification does not adequately describe the model (i.e. what were the default settings?) or how the mean relative abundances were calculated (i.e. compared to what reference population?). For example, looking at one of the claimed species, the abundance
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reported varies over at least an order of magnitude:
Thus, if the relative abundance of Eubacterium hallii is determined to be greater than 0.000783435 (see first dashed arrow) but lower than 0.001865504 (second dashed arrow) – is a diagnosis made? The specification does not sufficiently disclose what to do with this situation.
Therefore, it remains the Office’s position that the specification does not teach a skilled artisan, how to make and use the genus of methods claimed (i.e. how the 5 particular species of bacteria, in what samples, and/or by what means and/or compared to what reference population, and/or using what defaults and/or species in a Random Forest model and/or how to get the numbers in, for example, either Table 7 or Table 22, (which do not align) to predictably function (i.e. diagnose and treat autism in subjects with IBS), as is claimed. Accordingly, even a skilled artisan would require undue experimentation to practice the claimed methods because they would need to first determine several parameters for the model (by trial and error), in order to generate a mean relative abundance having six significant digits, in order to use the bacterial abundances, all based on haphazard selection and testing and confirmation of a diagnosis. They would also have to figure out, for themselves, what to do with the additional 10 (see claim 24), or additional 20 (see claim 25), or additional one or more (see claim 38) species abundances, and how to integrate that data into the method of diagnosing and treating autism in a subject with IBS.
Further, the specification does not sufficiently disclose methods of treating autism comprising administering any compositions that would increase the abundance of the 5 specific species and thus, does not teach how to make and/or use methods of treating autism in general, or by administering a nutraceutical, probiotic, or FMT, specifically. The specification does not teach how to make such compositions with the ability to target the 5 specific species and increase their abundances to thereby treat autism using compositions not otherwise art-recognized for treating autism. The specification does not sufficiently disclose how changing the abundances of the specific bacterial species thereby treats autism or how any change in as little as any one of them (increase or decrease) is indicative of the effectiveness of a treatment (see claim 33) because the specification does not sufficiently define of disclose what treating autism even requires or encompasses. Consequently, the specification does not sufficiently disclose methods of diagnosing and treating autism, in a subject with or without IBS, and thus cannot sufficiently disclose any methods of monitoring the effectiveness of such treatment (see claim 33). Accordingly, even a highly skilled artisan would require undue experimentation to practice the claimed methods because after figuring out how to diagnose autism (see above), they would then also need to determine how to treat autism, for example, what compositions could be used to increase the five particular bacterial species based on trial-and-error selection and testing and validating.
Therefore, the scope of the claims is extremely broad compared to the guidance and exemplification provided in the specification and the only way to determine if monitoring the relative abundances of the 5 specific species of bacteria, would predictably diagnose and treat autism, is empirical testing. Therefore, an undue amount of experimentation would be required to practice the invention, with any reasonable expectation of success, because testing such a vast number of options in an equally vast number of subjects, would be easily recognized by the skilled practitioner to be disproportionately demanding and thus rise to the level of non-routine.
State of the Prior Art and Level of Predictability in the Art: With regards to the state of the art, methods for diagnosing autism in subjects, with or without IBS, using microbial profiles, were under development, and thus were necessarily unpredictable, as evidenced by, the art of record.
For example, Srikantha et al. 2019 (The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorders; International Journal of Molecular Sciences; 20: 1-28). Srikantha teaches new research points to a possible link between autism spectrum disorders and gut microbiota (see abstract), but does not teach art-recognized methods for diagnosing autism using as little as a change in abundance of 5 particular species of bacteria. Srikantha teaches there are no satisfactory effective treatments available for autism (e.g. page 2, second paragraph). Srikantha teaches there are conflicting reports regarding the microbial compositions in autistic children (i.e. is under development; e.g. section 5.1 and Figure 3).
Similarly, Dan et al. 2020 (Altered gut microbial profile is associated with abnormal metabolic activity of Autism Spectrum Disorder; Gut Microbes 11(5): 1246-1267) teaches accumulating evidences demonstrates that gastrointestinal (GI) symptoms, such as gaseousness, diarrhea, and constipation, often co-occurred with ASD core symptoms in children with ASD; that recent studies have shown that changes in gut microbiota can modulate the gastrointestinal physiology, immune function, and even behavior through the gut-microbiome-brain axis; and these co-occurring gastrointestinal symptoms have prompted researchers to examine the gut microbial composition of ASD children and determine their potential role in promoting and reflecting ASD symptoms (see introduction and Figure 1). Dan teaches that compared to a control group, the ASD group displayed alternation of gut microbiota composition, including ASD showed less genera including Prevotella and Megamonas; and Escherichia-Shigella, Dialister, and Bifidobacterium were increased in ASD and that consistent with other studies that reported changes in microbiome associated with constipated populations, significant increases in the abundance of Coprobacter, Barnesiella, and Veillonella were found, but that Fusobacterium was reduced; and suggests the possibility that specific microbial patterns may be linked to constipation symptoms of specific disease, which suggests the necessity to more deeply understand the ASD-related gastrointestinal symptoms as they pertain to diagnosis and treatment of ASD (see Figures 5, 7 and Discussion). Thus, Dan supports methods for diagnosing and treating autism using microbial abundance data and/or profiles was under development and thus necessarily unpredictable.
Similarly, Olbjorn et al. 2019 (Fecal microbiota profiles in treatment-naïve pediatric inflammatory disease associations with disease phenotype, treatment, and outcome; Clinical and Experimental Gastroenterology 37-49; DOI: 10.2147/ CEG.S186235; of record) teaches Eubacterium hallii and Eubacterium rectale are associated with IBS (e.g. see table S1 and page 43); and therefore those subjects in Olbjoorn’s research paper, with a detectable reduction of E. halii (for example) would, using Applicant’s invention, risk be incorrectly diagnosed with and treated for autism. Thus, Olbjorn supports methods for diagnosing and treating autism using microbial abundance data and/or profiles was under development and thus necessarily unpredictable.
In addition, the state of the art does not recognize diagnosing or treating autism using microbial abundance data (i.e. the state of the art is unpredictable) but does recognize that miss diagnosing autism is harmful, as evidenced by, for example, Yates et al. 2016 (Diagnosing autism/autism spectrum disorders; Paediatrics and Child Health 26(12): 513-518) which teaches that to maximize detection and minimize harm it is essential for all clinicians working with children to have a sound knowledge of the presentation and assessment (i.e. diagnosis) of autism spectrum disorders (i.e. miss-diagnosing an ASD is harmful; see abstract). Yates teaches there are at least two international classification systems for diagnosing ASD comprising the use of a range of specifiers with the recognition that severity may vary with time and environmental context so should not be used to determine eligibility for and provision of services; and teaches specifiers including whether there is intellectual disability, language impairment, other associated disorders or comorbidities e.g. medical, genetic, mental or behavioral (see page 513, first page). Yates teaches ASD is a heterogeneous condition with no single pathognomonic feature or specific diagnostic test; and that diagnosis can be challenging as affected individuals display variation in the degree of behavioral severity, language and intellectual abilities (page 514). Yates teaches that age is an important factor in diagnosing autism (page 514, right column). Accordingly, Yates supports that the state of the art is unpredictable (i.e. under development and not agreed upon) and does not recognized diagnosing autism using microbial abundance data, but does recognize miss diagnosing is harmful and that age is an important consideration.
Similarly, Huang et al. 2020 (Diagnosing of autism in adulthood: A scoping review; Autism 24(6): 1311-1327) teaches adult autism assessment involves unique challenges because diagnosis relies on knowledge of developmental history, adults and families' lack of access to early medical records and inaccurate recall of developmental milestones which become significant difficulties (i.e. is unpredictable; e.g. see abstract and introduction). Huang teaches that considering the complex mental health needs of individuals diagnosed in adulthood and emotional reactions following diagnosis the lack of formal support after diagnosis is of concern especially as diagnostic services often do not provide ongoing support a collaborative multidisciplinary effort is needed to create support pathways after diagnosis and that even adults who were assessed but not diagnosed with autism would also benefit from counselling and mental health support due to high rates of mental illness and reported negative reactions following assessment (i.e. miss diagnosing an ASD is real because of the uncertainty and has harmful consequences). Accordingly, Huang also supports that the state of the art is unpredictable and does not recognized diagnosing autism using microbial abundance data, but does recognize miss diagnosing is harmful.
Finally, Kong et al. (2021) Nutrients 13, 1552 (submitted by Applicant) teaches the etiology of autism remains elusive and effective treatments are still largely unavailable (see Introduction, first paragraph) and that despite promising preliminary findings, the underlying mechanisms and causal relationships of such synergistic effects (i.e. for treatments) remain elusive and deserve further investigation in additional trials (is under development; e.g. see section 5, conclusions). Accordingly, Kong supports that the state of the art regarding treating autism is still under development and not agreed upon, and thus necessarily unpredictable.
Thus, the state of the art does not provide sufficient support for how a decrease in the abundances of Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea would be used for predictably, reliably, and/or accurately diagnosing, treating, and/or determining the effectiveness of treatment for subjects with autism, with or without IBS. Accordingly, the invention is not enabled because even the skilled artisan cannot make and use the invention, with a reasonable expectation of success, and without undue experimentation because of the lack of guidance on the reference population and/or how to generate the mean relative abundance data using a poorly describe model and/or how to use the generated abundance data to make a diagnosis and/or to treat and/or to monitor the effectiveness of treatments.
Relative Skill of Those in the Art: The relative level of skill of those in the art is deemed to be high (e.g. MD/PhD level professionals such as medical doctors, developmental pediatricians, psychiatrists, and neurologists); however, even one of these skill in the art could not predictably extrapolate the teachings in the specification, limited to lengthy lists of absolute and/or relative abundances of bacteria and/or genera determined via 16S DNA sequence analysis of fecal samples from human subjects compared to corresponding (but poorly disclosed reference) controls; to methods for specifically diagnosing and treating autism in subjects with IBS, using as little as the relative abundances of 5 particular species, in any sample, by any means, using any model, as broadly as is claimed. The skilled artisan simply cannot envision the structures required to make a diagnosis of and/or treatment of autism in subjects with IBS, thus conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used to determine such combinations or to test for such functional properties, after the fact (i.e. the ability to diagnose and treat and monitor would still need to be determined and verified empirically). Thus, even one of skill in the art, given its unpredictability, would have to engage in undue experimentation to determine how the relative abundances of 5 (and then potentially up to an additional 1-20) species’ would predictably retain the necessary functional properties (i.e. ability to diagnose and treat and monitor effectiveness of treatments of autism in subjects with IBS) and thereby carry out the invention as claimed.
Quantity of Experimentation Necessary Based on Content of the Disclosure: The specification does not enable the genus because where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims; In re Soil, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required; In re Fisher, 427 F.2d 833,839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity); see also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); and In re Vaeck, 947 F.2d 488,496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). Accordingly, without such guidance, the experimentation left to those skilled in the art is unnecessarily and improperly extensive and undue; emphasis added; See Amgen, Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F, 2d 1200, 18 USPQ 1016 (Fed. Cir. 1991) at 18 USPQ 1026 1027 and Exparte Forman, 230 USPQ 546 (BPAI 1986).
Consequently, in view of the lack of guidance and direction provided by Applicant there would be undue experimentation required to practice the invention, with a reasonable expectation of success and accordingly, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
Applicant’s Arguments and Response to Arguments
10. All of Applicant’s arguments have been considered but were not deemed persuasive; accordingly, the rejection is maintained for reasons of record. For the purpose of compact prosecution, it is noted that Applicant has set forth essentially the same arguments as before (including cutting and pasting past argument related to the original combination of 5 claimed species). Thus, only new arguments will be fully addressed, for all other arguments, and/or more detailed responses, please see Office Actions filed 05/30/25 and 09/23/25. For example:
With regards to the argument that the Examiner has not met the legal standard for lack of enablement (see Remarks, page 7 and again on page 18); the Office disagrees and invites Applicant to re-review the analysis of Wands Factors outlined above, as it unequivocally lays out that each factor weighs against enablement because each one supports how and why undue experimentation is required. Therefore, this repeated argument is misguided (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to the statement that “Contrary to the patent office, there are no sub-combinations as all five bacteria are measured…” (e.g. see Remarks, page 8); it is noted that the Office did not make this argument (i.e. Applicant is reminded of their amendments throughout prosecution; see also new objection made to claim 23). Therefore, this repeated argument is misguided (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to the statement “…the patent office has made no determination as to the breadth” (e.g. see Remarks, page 9); Applicant is again mistaken. It is noted that there is an entire section, with a bold heading, in every enablement rejection made and maintained. Therefore, this repeated argument is misguided (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to Applicant’s boilerplate summary for state of the art and level of predictability (see Remarks, page 9); it is noted that this argument is merely a series of generalizations and not specifically related to the claims or any facts in the instant case. In contrast, the Office set forth a detailed analysis with relevant art (see bolded title and section). Therefore, this argument is misguided.
With regards to the statement “… Applicants assert that all embodiments of the present claims are enabled, and the patent office has failed to prove otherwise”; (see Remarks, pages 9-10); the Office disagrees and Applicant is again invited to read this Action’s very detailed analysis of each and every Wands Factor. Therefore, this repeated argument is misguided (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to the smartHIT database (see Remarks page 12); Applicant is again remined that the database has not been disclosed and in order to meet enablement requirements anything essential to the claimed invention (e.g. the reference population and the data/model used), must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. Thus, this repeated argument still supports the Office’s position for lack of enablement of the instant specification (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to evidence found in Kong et al. 2021 (see Remarks, also page 12); it is noted that this paper supports the Office’s position that the state of the art regarding treating autism is still under development and thus necessarily unpredictable. Thus, this repeated argument supports the Office’s position (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to the arguments that misdiagnosing autism is not harmful (see Remarks, page 13); the Office disagrees, and notes this argument is not persuasive because these references (i.e. Yates and Huang) are used to support that diagnosing autism is still under development (e.g. not entirely agreed upon, resulting in misdiagnosing autism with harmful results) and thus is necessarily unpredictable.
With regards to Applicant’s attack of the references the Office cited (see Remarks, pages 10-13); the Office notes, none of these remarks are persuasive because they do not negate that the instant specification fails to sufficiently teach how to make and use the methods, without undue experimentation, as set forth previously, and maintained above. Therefore, this repeated argument is misguided (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to the statements “ … lack of working examples or lack of evidence that the claimed invention works as described should never be the sole reason for rejecting the claimed invention on the grounds of lack of enablement." In fact, "the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation." (see Remarks, page 14, emphasis added); it is noted that lack of working examples was not the sole reason set forth (i.e. every Wands Factor was analyzed) and, as set forth above, the invention is NOT otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. Thus, these arguments are misguided.
With regards to Example 11, Table 23, and the use of the “top 5 species” – including identifying the use of Eubacterium hallii, Eubacterium rectale, Lachnobacterium bovis, Lachnoclostridium glycyrrhizinilyticum, and Blautia glucerasea (see Remarks, pages 14-16); Applicant is reminded that they amended the claims such that the claims no longer require these “top 5” species, but rather another distinct combination of 5 species which were, apparently, indiscriminately selected from a list of 40-50 options. Thus, these repeated arguments all support the Office’s position for lack of enablement (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
With regards to the flood of references submitted by Applicant (see Remarks, page 13, and again on pages 16-18) is noted that none of the references show how the new, distinct, combination of 5 bacterial species accurately diagnoses and treats autism in general, or specifically in a human subject with IBS; nor do any of the references provide the essential reference population data; nor do any of the references address the appropriate models and/or parameters thereof. Thus, none of these arguments are germane.
With regards to the argument that a skilled person could readily select probiotics or other energy sources, and test them, in order identify appropriate therapeutic products to alter the abundance of the 5 bacterial species listed in the claims; (see Remarks, page 18); the Office disagrees and notes that these arguments do not address the diagnostic requirements for the claims; and that these arguments support the insufficiency of the as filed specification for methods of treatment because the skilled artisan would have to "figure out" how to treat the subject. Therefore, this repeated argument is misguided (see additional comments under “Responses to Arguments” in Office Actions filed 05/30/25 and 09/23/25).
Accordingly, all of Applicant’s arguments have been fully considered but were not deemed persuasive because several of them do not even apply to the claims, as amended (e.g. the new combination of 5 particular bacteria, that are NOT the top 5 identified on the poorly described list); and/or they do not address all of the issues raised in the rejection (e.g. the poorly described reference population data and/or model). Further, it is the Office’s position that the Wands Factor Analysis set forth by Applicant, does not outweigh the Wands Factor Analysis set for by the Office. Consequently, the rejection is maintained for reasons of record, (see additional comments in Responses to Arguments filed 05/30/25 and 09/23/25).
New Rejections Necessitated by Applicant’s Amendments
New Rejection: Claim Rejections - 35 USC § 112
11. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
12. Claims 23-25, 30-33, and 37-38 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The newly amended claims now encompass the use of a particular combination of five bacterial species: Eubacterium hallii, Eubacterium desmolans, Anaerostipes coli, Faecalibacterium prausnitzii, and Blautia glucerasea to diagnose and treat autism in a human subject with IBS. However, the specification does not describe this particular combination of 5 bacteria (i.e. the original 5 claimed bacteria were found in paragraph [0038]) for diagnosing and treating autism in a subject with IBS; and thus the specification per se supplies evidence that, at the time of filing, this particular grouping (i.e. the combination of these particular 5 species) haphazardly selected from Table 22 was not envisaged from a list of 50 ranked species in Table 22. Accordingly, it is the Office’s position that these newly added claim amendments constitute new matter.
Although the PTO has the initial burden of presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims, when filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP 714.02 and 2163.06 (“Applicant should therefore specifically point out the support for any amendments made to the disclosure.”). It is noted that Applicant did not point to support in the specification, by page and line number, for the new limitations in the amended claims, but only stated that “Support for the amendments to claim 23 can be found throughout the specification and at least in Table 22” (see Remarks page 4).
However, as set forth above, the instant specification, including Table 22, does not envisage the use of as little as this particular combination of 5 specific species. Accordingly, the newly added limitations in the claims constitute new matter.
Conclusion
13. No claims are allowed.
14. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
15. A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http: //www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker can be reached on (571)-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY MAILLE LYONS/Examiner, Art Unit 1645
March 23, 2026